Early Treatment Stratification Based on PET Scan Response to Chemotherapy in Patients With Diffuse Large B-cell Lymphoma

Diffuse Large B-cell Lymphoma Clinical Trial

— R-MEGACHOP  

Official title:

Early Treatment Stratification Based on PET Scan Response to R-MEGACHOP Followed by R-MEGACHOP or R-IFE Plus Peripheral Autologous Stem Cell Transplant (PBSCT) in Patients With Poor Prognosis DLBCL

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01361191
• Other study ID #: GEL/TAMO-2006
• Secondary ID: EudraCT number 2
• Status: Completed
• Phase: Phase 2
• First received: April 14, 2008
• Last updated: October 29, 2013
• Start date: June 2007
• Est. completion date: September 2012

Study information

• Verified date: October 2013
• Source: Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial Summary

The aim of the study is to evaluate the event free survival at three years in patients with diffuse large B-cell lymphoma with poor prognostic factors receiving R-MegaCHOP as induction therapy. Patients with positive PET after three cycles of R-MegaCHOP receive early salvage treatment with R-IFE and autologous stem cell transplantation. Patients with negative PET after three cycles of R-MegaCHOP are treated with three additional cycles of R-MegaCHOP without transplant.

Description:

In addition to the above:

• To evaluate the overall survival after three years.

• To determine the rate of global responses and complete remissions, uncertain and partial.

• To determine the duration of the complete response after the treatment termination.

• To carry out an exploratory follow up of the event free survival and the overall survival at 5 years.

• To evaluate the treatment toxicity according CTC criteria (version 3.0) of the National Cancer Institute (NCI).

• To asses the role of PET in the disease stage and response evaluation compared to CAT.

• To identify the predictable response factors after 6 cycles of treatment with R-MegaCHOP administrated every 21 days; or 3 cycles of R-MegaCHOP, followed by IFE+TAPH in patients with DLBCL of severe prognosis.

• To evaluate the therapeutic fulfillment of the R-MegaCHOP and R+IFE cycles of treatment and/or R-IFE in reference with delays with the cycles administration and reductions of the chemotherapy dose (planned dose administrated in the planned term).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: September 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. follicular lymphoma grade III diagnosed patients, diffuse large B-cell lymphoma, histologically confirmed with CD20+

2. aged between 18 and 65 years. Patients aged from 65 to 70 years can be included according to the investigator's criteria regarding the patients' global health status and the absence of excluding comorbidity.

3. IPI adjusted to the age over 1 or a-IPI and beta2-microglobulin equal or higher than 3 mg/dl 3. Punctuation in the ECOG grade from 0 to 4

4. Life expectancy over 12 weeks

5. Written informed consent form 6. New diagnosed patient without any previous treatment

Exclusion Criteria:

1. Existence of severe cardiac, pulmonary, neurologic, psychiatric and metabolic diseases not caused by the lymphoma.

2. uncontrolled high blood pressure (diastolic pressure in rest > 115 mmHg)

3. Altered hepatic function (bilirubin or AST/ALT superior or equal at 2 times the superior limit of normality) or renal (creatinine equal or superior at 1.5 times the superior limit of normality) not caused by the lymphoma.

4. other malignant neoplasias along the past 5 years, except skin tumors, excluded melanoma or carcinoma in situ of cervix

5. patients positive for HIV

6. patients with transformed follicular lymphoma

7. pregnant women or in nursing; women of childbearing age who do not use an adequate contraceptive method before being included in the study

8. ventricular ejection fraction inferior to 50%

9. patients with severe psychiatric diseases which can interfere with their ability for understanding the study (including alcoholism or drug addiction)

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diffuse Large B-cell Lymphoma
• Follicular Grade 3B Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• R-MEGACHOP
If PET + after third cycle: 2 cycles of R-IFE followed by PBSCT If PET - after third cycle: 3 additional cycles of R-MegaCHOP - R-MegaCHOP: cycles every 21 days RITUXIMAB Dosage: 375mg/m2, IV, day 1 CICLOPHOSPHAMIDE Dosage: 1500 mg/m2, IV, day 1 DOXORUBICIN Dosage: 65 mg/m2, IV, day 1 VINCRISTIN: Dosage 1.4 mg/m2 (max. 2.0 mg/m2, IV, day 1 PREDNISONE Dosage: 60 mg/m2, IV, day 1-5 R-IFE: 2 cycles every 21 days: IFOSFAMIDE Dosage: continuous perfusion of 10 gr/m2/iv during 72 hours. Therefore, 3.33 gr/m2/corporal weight 24 hours day +1, +2 and +3. ETOPOSIDE Dosage: total 900 mg/m2, IV, which is 150 mg/m2 during 12 hours (days +1, +2 and +3).

Locations

Country	Name	City	State
Spain	ICO- Hospital Duran i Reynals	Hospitalet de Llobregat	Barcelona
Spain	Complejo Hospitalario de Jaén	Jaén
Spain	Hospital de Jerez	Jerez de la Frontera	Cádiz
Spain	Hospital Universitario de Canarias	La Laguna	Santa Cruz de Tenerife
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario La Princesa	Madrid
Spain	Hospital Univ. Morales Meseguer	Murcia
Spain	Hospital Son Llàtzer	Palma de Mallorca	Mallorca
Spain	Hospital Univ. Son Dureta	Palma de Mallorca	Mallorca
Spain	Clínica Universitaria de Navarra	Pamplona
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Marques de Valdecilla	Santander
Spain	Hospital Clínico Univ. de Santiago	Santiago de Compostela	Galicia
Spain	Hospital General de Segovia	Segovia
Spain	Hospital Universitario Río Hortega	Valladolid
Spain	Hospital Universitario Virgen de la Concha	Zamora
Spain	Hospital Clínico Lozano Blesa	Zaragoza

Sponsors (1)

Lead Sponsor	Collaborator
Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event free survival at 3y in pat with DLBCL with a-IPI>1 or a-IPI=1 and ß2 µglobulin>=3mg/dl in pat PET+ after 3cycles of R-MegaCHOP and early rescue with R-IFE+TAPH or in pat PET- after 3cycles R-MegaCHOP followed by 3cycles of R-MegaCHOP without TAPH		5 years follow-up	Yes
Secondary	To evaluate the overall survival after three years. Further secondary outcomes as described in study summary.		5 years follow-up	Yes